Molecular and Cellular Physiology and Biophysics of the Heart

Molecular and Cellular Physiology and Biophysics of the Heart

Heart disease is the biggest killer in the society today. The function of the heart is governed by the cell biology and molecular physiology of the heart muscle. As such, the heartbeat, the rhythm, the force of the contraction, and irregularities thereof are controlled by the network of cells that make up the heart. In my laboratory, we study the heart muscle and its constituent cells under normal conditions, during pathologic conditions such as myocardial infarction, heart failure, and cardiac myopathies, as well as after exercise training in both health and disease. We do this to understand the heart better, and therefore be able to generate better therapies for the heart when something goes wrong and ultimately to reduce the impact of heart disease to the patient as well as the society as a whole. This includes studying the cellular and molecular events that underlie and translate into first a reduced and secondly an improved function. In order to do this, we employ a range of experimental models that mimic normal function, dysfunction, disease and exercise, as well as physiological, biophysical, electrophysiological, biochemical, and molecular laboratory methods.

Heart disease is the leading cause of disability and death in the western world including the UK, with a limited scope for treatment. The 5-year mortality of heart failure; a severe form of heart disease is 50-70%, of which ~50% die of progressive pump failure chiefly caused by abnormal contractile function and ~50% of sudden arrhythmic events. Both abnormal contractile function and many arrhythmic events are further mechanistically explained by abnormalities in cardiomyocyte excitation-contraction coupling. Excitation-contraction coupling is initiated by the sarcolemmal and transverse tubule depolarisation that activates the voltage-sensitive L-type Ca2+ channels; this inward Ca2+ current causes further Ca2+ release from the sarcoplasmic reticulum via the Ca2+ channel ryanodine receptor-2, and the resultant increase of the intracellular Ca2+ concentration evokes myofilaments contraction (systole). The activities of the sarcoplasmic reticulum Ca2+ ATPase SERCA2a and the sarcolemmal Na+/Ca2+-exchanger restore the cytoplasmic Ca2+ to resting levels (diastole). All of the proteins involved may be modulated by different small molecules that interact with the excitation-contraction coupling process. Cardiac contraction is directly governed by this process, but certain ventricular arrhythmias are also initiated by aberrant sarcolemmal and intracellular control of the ions involved in excitation-contraction coupling such as Ca2+, Na+, and K+.

For this reason, understanding, modulating, and therapeutically intervening with the excitation-contraction coupling process or the small molecules that interact with it becomes important, in order to reduce the burden of heart disease and failure. This therefore has consequences for the individual heart disease patients and the society alike, especially as the management of heart disease is costly and strains economies from households to national GDPs. Thus, the socioeconomic consequences of the heart failure pandemic are enormous and need be dealt with by more affordable solutions.

Importantly, exercise training provides an inexpensive and underdeveloped benefit to the patient because it physiologically improves the function of the heart directly through its modulation of excitation-contraction coupling and indirectly through its modulation of small molecules that subsequently interact with excitation-contraction coupling. Therefore, exercise training improves the function and control of the heart, which has been evidenced to support both athletes seeking to improve sporting performance, regular healthy individuals seeking to improve work capacity for daily functioning, and patients with heart and other cardiovascular diseases, hypertension, diabetes, metabolic syndrome and disease, muscle disorder, and several other dysfunctions.

Therefore, a detailed examination of cardiac function and cardiomyocyte biology in normal, dysfunctional, and failing hearts in the absence and presence of exercise training is necessary to understand how cardiac health may be modulated to benefit individuals, patients and the society, by exercise training as an affordable complementary option to other established treatments. Secondly, this research also has the power to reveal molecular aims for improving cardiac health that may be targeted by new experimental interventions.


  1. Kemi OJ, Haram PM, Hoydal MA, Wisloff U, Ellingsen O. Exercise training and losartan improve endothelial function in heart failure rats by different mechanisms. Scand Cardiovasc J 2013 Jan 3 [Epub ahead of print]
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  20. Bye A, Hoydal MA, Catalucci D, Langaas M, Kemi OJ, Beisvag V, Koch LG, Britton SL, Ellingsen O, Wisloff U. Gene expression profiling of skeletal muscle in exercise-trained and sedentary rats with inborn high and low VO2max. Physiol Genomics 2008;35:213-221.
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  22. Kemi OJ, Rognmo O, Wisloff U, Haram PM. Exercise training does / does not induce vascular adaptations beyond the active muscle beds. J Appl Physiol 2008;105:1008-1009.
  23. Tjonna AE, Lee SJ, Rognmo O, Stolen TO, Bye A, Haram PM, Loennechen JP, Al-Share QY, Skogvoll E, Slordahl SA, Kemi OJ, Najjar SM, Wisloff U. Aerobic interval training versus continuous moderate exercise as a treatment for the metabolic syndrome – a pilot study. Circulation 2008;118:346-354.
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  37. Haram PM, Adams V, Kemi OJ, Brubakk AO, Hambrecht R, Ellingsen O, Wisloff U. Time-course of endothelial adaptation following acute and regular exercise. Eur J Cardiovasc Prev Rehabil 2006;13:585-591.
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  41. Kemi OJ, Haram PM, Loennechen JP, Osnes JB, Skomedal T, Wisloff U, Ellingsen O. Moderate vs. high exercise intensity: differential effects on aerobic fitness, cardiomyocyte contractility, and endothelial function. Cardiovasc Res 2005;67:161-172.
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  43. Kemi OJ, Hoff J, Engen LC, Helgerud J, Wisloff U. Soccer specific testing of maximal oxygen uptake. J Sports Med Phys Fitness 2003;43:139-144.
  44. Kemi OJ, Loennechen JP, Wisloff U, Ellingsen O. Intensity-controlled treadmill running in mice: Cardiac and skeletal muscle hypertrophy. J Appl Physiol 2002;93:1301-1309.
  45. Hoff J, Wisloff U, Engen LC, Kemi OJ, Helgerud J. Soccer specific aerobic endurance training. Br J Sports Med 2002;36:218-221.
  46. Wisloff U, Helgerud J, Kemi OJ, Ellingsen O. Intensity-controlled treadmill running in rats: VO2max and cardiac hypertrophy. Am J Physiol Heart Circ Physiol 2001;280:H1301-H1310.